Ketals keto groups

The most commonly used protected derivatives of aldehydes and ketones are 1,3-dioxolanes and 1,3-oxathiolanes. They are obtained from the carbonyl compounds and 1,2-ethanediol or 2-mercaptoethanol, respectively, in aprotic solvents and in the presence of catalysts, e.g. BF, (L.F. Fieser, 1954 G.E. Wilson, Jr., 1968), and water scavengers, e.g. orthoesters (P. Doyle. 1965). Acid-catalyzed exchange dioxolanation with dioxolanes of low boiling ketones, e.g. acetone, which are distilled during the reaction, can also be applied (H. J. Dauben, Jr., 1954). Selective monoketalization of diketones is often used with good success (C. Mercier, 1973). Even from diketones with two keto groups of very similar reactivity monoketals may be obtained by repeated acid-catalyzed equilibration (W.S. Johnson, 1962 A.G. Hortmann, 1969). Most aldehydes are easily converted into acetals. The ketalization of ketones is more difficult for sterical reasons and often requires long reaction times at elevated temperatures. a, -Unsaturated ketones react more slowly than saturated ketones. 2-Mercaptoethanol is more reactive than 1,2-ethanediol (J. Romo, 1951 C. Djerassi, 1952 G.E. Wilson, Jr., 1968). 

The hydrogenation of 5a-cholestanone (58) in methanolic hydrobromic acid over platinum gives 3j5-methoxycholestane ° (61). This compound is also obtained from the palladium oxide reduction of (58) in methanol in the absence of acid. Hydrogenation of 5 -cholestanone also gives the 3j5-methoxy product under these conditions. Reduced palladium oxides are quite effective for the conversion of ketones to ethers. The use of aqueous ethanol as the solvent reduces the yield of ether. Ketals are formed on attempted homogeneous hydrogenation of a 3-keto group in methanol. ... 

The 1,4-reduction of an enone in the presence of a ketal is shown in Eq. 275.436 The Et3SiH/TFA system reduces the polyfunctional cyclic ,/3-enone in Eq. 276 without affecting the c/-hydroxy carboxyl or a-chloro keto groups.453... 

Another way of avoiding reduction of the keto group in a keto ester is protection by acetalization. Ketals are evidently not reduced by lithium... 

The decarboxylation of diacyl peroxides was also applied in the synthesis of cydopentadecanone, a compound with a musky odor of interest in the perfume industry (Scheme 2.31) [62].The photolysis of tetraacyl diperoxides 119 led to the extrusion of four molecules of C02 to give 121 in 73% yield. When decarboxylation occurred thermally, the product was obtained in only 41% yield. While the diacyl peroxide containing a keto group (106) was shown to give side products, the ketal-protected diperoxide 120 decarboxylated efficiently to give 122 in 65% yield. 

Selective enone ketalization. The reaction of ethylene glycol catalyzed by pyri-dinium p-toluenesulfonate (PPTS) does not discriminate between saturated and a, 3-unsaturated ketones. In contrast, this hindered pyridinium salt (1) permits selective ketalization of enones in the presence of saturated keto groups. 2,6-Lutidinium p-toluenesulfonate (2) is as effective. 

Since 2-acetylphenothiazine undergoes an autocondensation with sodamide, the introduction of a substituent in position 10 using this base as condensing agent requires protection of the keto group. This may be achieved by ketalization with ethylene glycol or by conversion into Schiff bases derivatives stable in alkaline medium are thus obtained, from which the ketones may be liberated by acidification after A-alkylation. 

The keto group of acetoacetic ester is protected as the ethylene ketal -during the reduction of the ester by sodium and alcohol. Hydrolysis of the ketal by acid then gives l-hydroxy-3-butanone in 44% over-all yield. ... 

The presence of an a, -conjugated double bond noticeably reduces the electrophilic activity of a carbonyl carbon. This effect allows one to protect, selectively, an isolated keto group as a ketal in the presence of a conjugated enone moiety. Thus, the selective transformations of conjugated enones, a situation frequently encountered in steroid chemistry, are achieved in this manner. 

Engel and Rakhit found that selective ketalization of the 12-keto group of the 12,20-diketone (1) by reaction with ethylene glycol and boron trifluoride etherate proceeds best with methylene chloride present as co-solvent to provide a homogeneous medium. Without the cosolvent, the yield was 57%. 

Carbonyl compounds (after ref. 5]. McMurry58 desired to selectively reduce an olefinic double bond with diborane in the presence of a keto group. This was successfully achieved by conversion to the dinitrophenylhydrazone, hydroboration and removal of the protective group by ozonolysis in ethyl acetate at — 78°. Oximes and oxime acetates are reduced by BH3. Attempted protection by ketalization in this case was unsuccessful because of simultaneous migration of the double bond. 

C2I can be carried out and then the parent A4-3-keto system (1) is regenerated by the action of mild alkali. A British group46 prepared the 17-ethylene acetal of A4-andro-stene-3,11,17-trione by conversion to the eniminium salt (2) to protect the A4-3-keto grouping, ketalization with ethylene glycol (p-TsOH), and hydrolysis of the protective group. The overall yield was 72%. Direct ketalization of a 17-ketone had been effected earlier with ethylene glycol, but the yield was in the order of 25%. 

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